Pre-clinical data show that estrogen increases the likelihood of stimulant self- administration;progesterone has the opposite effect and can reverse the effect of estradiol. Limited human data show that progesterone attenuates cravings for and subjective positive response to stimulants in women. Pregnancy, which is characterized by high circulating progesterone levels, is associated with decreased substance use. Unfortunately, drug use increases again after delivery. The incremental decrease in drug use over the course of pregnancy as progesterone levels increase, and the escalation in drug use after delivery when progesterone levels drop, suggests the possibility that progesterone influences drug use. This application seeks funding to obtain preliminary data on whether treatment with progesterone, which would counterbalance the progesterone lost with parturition, reduces cocaine use among postpartum women. Accordingly, we propose a double-blind, randomized, placebo-controlled trial that would obtain preliminary data on the efficacy of oral micronized progesterone for postpartum women with a history of cocaine dependence or abuse. We would randomize 50 postpartum women and evaluate them weekly for three months and then again 3 months after the end of the trial. Participants would also receive cognitive-behavioral counseling for drug use. Outcome measures include the percentage of days and amount of cocaine use during the trial for women randomized to one or the other of the two (placebo or progesterone) conditions. PUBLIC HEALTH RELEVANCE: Pregnancy, which is characterized by high circulating progesterone levels, is associated with decreased substance use. This application seeks funding to obtain preliminary data on whether treatment with progesterone, which would counterbalance the progesterone lost with parturition, reduces cocaine use among postpartum women. Accordingly, we propose a double-blind, randomized, placebo- controlled trial that would obtain preliminary data on the efficacy of oral micronized progesterone for postpartum women with a history of cocaine dependence or abuse.